Talc pleurodesis: Evidence of systemic Inflammatory response to small size talc particles

The mechanisms of the systemic response associated with talc-induced pleurodesis are poorly understood. The aim of this study was to assess the acute inflammatory response and migration of talc of small. size particles injected in the pleural space. Rabbits were injected intrapleurally with talc solution containing small. or mixed particles and blood and pleural fluid samples were collected after 6, 24 or 48 h and assayed for leukocytes, neutrophils, lactate dehydrogenase, IL-8, VEGF, and TGF-beta. The lungs, spleen, liver and kidneys were assessed to study deposit of talc particles. Both types of talc produced an acute serum inflammatory response, more pronounced in the small particles group. Pleural fluid IL-8 and VEGF levels were higher in the small particle talc group. Correlation between pleural VEFG and TGF-beta levels was observed for both groups. Although talc particles were demonstrated in the organs of both groups, they were more pronounced in the small talc group. In conclusion, intrapleural injection of talc of small size particles produced a more pronounced acute systemic response and a greater deposition in organs than talc of mixed particles. (C) 2008 Elsevier Ltd. All rights reserved.State of Sao Paulo Research woundation (FAPESP)National Board of Scientific and Technologic Development (CNPq), Brazil

The effects of benralizumab on airway geometry and dynamics in severe eosinophilic asthma: a single-arm study design exploring a functional respiratory imaging approach

Abstract Background Severe eosinophilic asthma (SEA) is characterised by elevated blood/sputum eosinophil counts and airway inflammation, which can lead to mucus plug-mediated airway obstruction, increased exacerbation frequency, declines in lung function, and death. Benralizumab targets the alpha-subunit of the interleukin-5 receptor found on eosinophils, leading to rapid and near complete eosinophil depletion. This is expected to result in reduced eosinophilic inflammation, reduced mucus plugging and improved airway patency and airflow distribution. Methods BURAN is an interventional, single-arm, open-label, uncontrolled, prospective, multicentre study during which participants will receive three 30 mg subcutaneous doses of benralizumab at 4-week intervals. This study will use functional respiratory imaging (FRI), a novel, quantitative method of assessing patients’ lung structure and function based on detailed, three-dimensional models of the airways, with direct comparison of images taken at Weeks 0 and 13. Patients aged ≥ 18 years with established SEA who may be receiving oral corticosteroids and/or other asthma controller medications, who are inadequately controlled on inhaled corticosteroid-long-acting β2-agonist therapies and who have had ≥ 2 asthma exacerbations in the previous 12 months will be included. The objectives of BURAN are to describe changes in airway geometry and dynamics, measured by specific image-based airway volume and other FRI endpoints, following benralizumab therapy. Outcomes will be evaluated using descriptive statistics. Changes in FRI parameters, mucus plugging scores and central/peripheral ratio will be quantified as mean percent change from baseline (Week 0) to Week 13 (± 5 days) and statistical significance will be evaluated using paired t-tests. Relationships between FRI parameters/mucus plugging scores and conventional lung function measurements at baseline will be assessed with linear regression analyses for associations between outcomes, scatterplots to visualise the relationship, and correlation coefficients (Spearman’s rank and Pearson’s) to quantify the strength of these associations. Conclusions The BURAN study will represent one of the first applications of FRI—a novel, non-invasive, highly sensitive method of assessing lung structure, function and health—in the field of biologic respiratory therapies. Findings from this study will increase understanding of cellular-level eosinophil depletion mechanisms and improvements in lung function and asthma control following benralizumab treatment. Trial registration EudraCT: 2022-000152-11 and NCT0555250

Monoclonal anti-vascular endothelial growth factor antibody reduces fluid volume in an experimental model of inflammatory pleural effusion

Background and objective: Vascular endothelial growth factor (VEGF) is known to increase vascular permeability and promote angiogenesis. It is expressed in most types of pleural effusions. However, the exact role of VEGF in the development of pleural effusions has yet to be determined. The anti-VEGF mAb, bevacizumab, has been used in the treatment of cancer to reduce local angiogenesis and tumour progression. This study describes the acute effects of VEGF blockade on the expression of inflammatory cytokines and pleural fluid accumulation. Methods: One hundred and twelve New Zealand rabbits received intrapleural injections of either talc or silver nitrate. In each group, half the animals received an intravenous injection of bevacizumab, 30 min before the intrapleural agent was administered. Five animals from each subgroup were sacrificed 1, 2, 3, 4 or 7 days after the procedure. Twelve rabbits were used to evaluate vascular permeability using Evans`s blue dye. Pleural fluid volume and cytokines were quantified. Results: Animals pretreated with anti-VEGF antibody showed significant reductions in pleural fluid volumes after talc or silver nitrate injection. IL-8 levels, vascular permeability and macroscopic pleural adhesion scores were also reduced in the groups that received bevacizumab. Conclusions: This study showed that bevacizumab interferes in the acute phase of pleural inflammation induced by silver nitrate or talc, reinforcing the role of VEGF as a key mediator in the production of pleural effusions. The results also suggest that bevacizumab should probably be avoided in patients requiring pleurodesis.Foundation to Support Research of the State of Sao Paulo (FAPESP)National Council of Research (CNPq), Brazi

Predictive models for diagnosis of pleural effusions secondary to tuberculosis or cancer

Background and objective: Tuberculosis (TB) and cancer are two of the main causes of pleural effusions which frequently share similar clinical features and pleural fluid profiles. This study aimed to identify diagnostic models based on clinical and laboratory variables to differentiate tuberculous from malignant pleural effusions. Methods: A retrospective study of 403 patients (200 with TB; 203 with cancer) was undertaken. Univariate analysis was used to select the clinical variables relevant to the models composition. Variables beta coefficients were used to define a numerical score which presented a practical use. The performances of the most efficient models were tested in a sample of pleural exudates (64 new cases). Results: Two models are proposed for the diagnosis of effusions associated with each disease. For TB: (i) adenosine deaminase (ADA), globulins and the absence of malignant cells in the pleural fluid; and (ii) ADA, globulins and fluid appearance. For cancer: (i) patient age, fluid appearance, macrophage percentage and presence of atypical cells in the pleural fluid; and (ii) as for (i) excluding atypical cells. Application of the models to the 64 pleural effusions showed accuracy higher than 85% for all models. Conclusions: The proposed models were effective in suggesting pleural tuberculosis or cancer

Pleural fluid: Are temperature and storage time critical preanalytical error factors in biochemical analyses?

Background: Biochemical analysis of fluid is the primary laboratory approach hi pleural effusion diagnosis. Standardization of the steps between collection and laboratorial analyses are fundamental to maintain the quality of the results. We evaluated the influence of temperature and storage time on sample stability. Methods: Pleural fluid from 30 patients was submitted to analyses of proteins, albumin, lactic dehydrogenase (LDH), cholesterol, triglycerides, and glucose. Aliquots were stored at 21 degrees, 4 degrees, and-20 degrees C, and concentrations were determined after 1, 2, 3, 4, 7, and 14 days. LDH isoenzymes were quantified in 7 random samples. Results: Due to the instability of isoenzymes 4 and 5, a decrease in LDH was observed in the first 24 h in samples maintained at -20 degrees C and after 2 days when maintained at 4 degrees C. Aside from glucose, all parameters were stable for up to at least day 4 when stored at room temperature or 4 degrees C. Conclusions: Temperature and storage time are potential preanalytical errors in pleural fluid analyses, mainly if we consider the instability of glucose and LDH. The ideal procedure is to execute all the tests immediately after collection. However, most of the tests can be done in refrigerated sample;, excepting LDH analysis. (C) 2010 Elsevier B.V. All rights reserved.Research Support Foundation for the State of Sao Paulo (FAPESP)National Research Council (CNPq), Brazi

Clinical usefulness of B-type natriuretic peptide in the diagnosis of pleural effusions due to heart failure

Background and objective: Light`s criteria are frequently used to evaluate the exudative or transudative nature of pleural effusions. However, misclassification resulting from the use of Light`s criteria has been reported, especially in the setting of diuretic use in patients with heart failure (HF). The objective of this study was to evaluate the utility of B-type natriuretic peptide (BNP) measurements as a diagnostic tool for determining the cardiac aetiology of pleural effusions. Methods: Patients with pleural effusions attributable to HF (n = 34), hepatic hydrothorax (n = 10), pleural effusions due to cancer (n = 21) and pleural effusions due to tuberculosis (n = 12) were studied. Diagnostic thoracentesis was performed for all 77 patients. Receiver operating characteristic (ROC) curves were constructed to determine the diagnostic accuracy of plasma BNP and pleural fluid BNP for the prediction of HF. Results: The areas under the ROC curves were 0.987 (95% CI 0.93-0.998) for plasma BNP and 0.949 (95% CI 0.874-0.986) for pleural fluid BNP, for distinguishing between patients with pleural effusions caused by HF (n = 34) and those with pleural effusions attributable to other causes (n = 43). The cut-off concentrations with the highest diagnostic accuracy for the diagnosis of HF as the cause of pleural effusion were 132 pg/mL for plasma BNP (sensitivity 97.1%, specificity 97.4%) and 127 pg/mL for pleural fluid BNP (sensitivity 97.1%, specificity 87.8%). Conclusions: In patients with pleural effusions of suspected cardiac origin, measurements of BNP in plasma and pleural fluid may be useful for the diagnosis of HF as the underlying cause.Foundation to Support Research from the State of Sao Paulo (FAPESP)National Board of Scientific and Technologic Development (CNPq

Pleurodesis induced by intrapleural injection of silver nitrate or talc in rabbits: can it be used in humans? Pleurodese induzida pela injeção intrapleural de nitrato de prata ou talco em coelhos: há perspectivas para o uso em humanos?

OBJECTIVE: To evaluate the pleuropulmonary alterations caused by intrapleural injection of silver nitrate or talc in an experimental model, in order to consider its use in human beings. METHOD: 112 rabbits were randomly selected to receive intrapleural 0.5% silver nitrate or 400 mg/kg talc slurry in 2 ml saline. Eight rabbits of each group were sacrificed after 1, 2, 4, 6, 8, 10, or 12 months. Regarding the pleural cavity, the degree of macroscopic pleurodesis (adherences) and microscopic alterations, represented by inflammation and pleural fibrosis, were analyzed. The parenchyma was evaluated regarding the degree of alveolar collapse, intra-alveolar septum edema, and cellularity, on a 0 to 4 scale. RESULTS: Intrapleural injection of silver nitrate produced earlier and more intense pleurodesis than talc slurry injection. The parenchymal damage was more evident with silver nitrate, considered as moderate, and limited to the first evaluation (after one month). From the second month on and throughout the entire one-year follow-up, the parenchymal damage was similar with both substances, only the pleural adherences were more intense with silver nitrate. CONCLUSIONS: Intrapleural silver nitrate produces better and longer-lasting than intrapleural talc injection. The parenchymal alterations, although discreet, are more pronounced when silver nitrate is used, but minimal after two months, and similar to those produced by talc injection during the entire one-year observation period. These effects on the pulmonary parenchyma do not contraindicate the use in humans. Thus, the use of intrapleural silver nitrate to produce fast and effective pleurodesis can be considered in patients in which pleural cavity symphysis is desired.<br>OBJETIVO DE ESTUDO: Avaliar as alterações pleuropulmonares causadas pela injeção intrapleural de talco ou nitrato de prata em modelo experimental, com o intuito de considerar sua utilização em humanos. MÉTODO: 112 coelhos foram aleatoriamente escolhidos para receber, no espaço pleural, 400mg/kg de talco em 2ml de solução salina ou 2ml de nitrato de prata a 0,5%, sendo oito animais, em cada grupo, sacrificados após um, dois, quatro, seis, oito, 10 ou 12 meses. Em relação à cavidade pleural, foram analisados o grau de pleurodese macroscópica (aderências) e as alterações microscópicas representadas por inflamação e fibrose dos folhetos pleurais. O parênquima foi avaliado quanto ao grau de colapso alveolar, edema dos septos interalveolares e celularidade em escore de 0 a 4. RESULTADOS: A injeção intrapleural de nitrato de prata produziu pleurodese mais precoce e mais intensa do que a injeção de talco. A lesão parenquimatosa foi mais evidente com nitrato de prata, sendo considerada de grau moderado e restrita à primeira avaliação (um mês). A partir do segundo mês, e durante todo o seguimento de um ano, a lesão parenquimatosa foi semelhante com ambas as substâncias, sendo apenas as aderências pleurais mais intensas com nitrato. CONCLUSÕES: O nitrato de prata intrapleural produz melhor e mais duradoura pleurodese do que a injeção intrapleural de talco. As alterações parenquimatosas, apesar de discretas, são mais pronunciadas com o uso de nitrato de prata, sendo, porém, mínimas após dois meses e semelhantes, durante todo o período de observação de um ano, às encontradas com o uso do talco. Esses efeitos sobre o parênquima pulmonar não contra-indicam seu uso em seres humanos. Dessa forma, o uso do nitrato de prata intrapleural, com o intuito de produzir rápida e efetiva pleurodese, pode ser considerado nos pacientes em que se deseja a sínfise da cavidade pleural